Infant Sero-protection: Comparing Antiretroviral therapy, Maternal and Infant Factors Influence on Infant HIV acquisition in Uganda: A six-year Real-World Perspective

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Abstract Background Prevention of mother-to-child transmission of HIV (PMTCT) remains a critical pillar in reducing new paediatric HIV infections. While Antiretroviral Therapy (ART) scale-up has significantly reduced transmission, differential effectiveness of ART regimens, maternal and infant factors within PMTCT programs remain underexplored. This study examined the comparative influence of ART, maternal and infant factors on the risk of infant HIV seroconversion. Methods We retrospectively reviewed records of 962 HIV-exposed infants (918 mother-infant pairs and 44 without maternal data) from the Mildmay Uganda PMTCT clinic. Infant HIV serostatus was analyzed in relation to ART, maternal, and infant characteristics. Descriptive statistics summarized the data; associations were tested using Chi-square and Fisher’s exact tests. Bivariate and multivariable logistic regression identified predictors. The maternal and infant models were compared using log-likelihood, Akaike Information Criterion (AIC), and Bayesian Information Criterion (BIC) statistics. Results Overall HIV seropositivity among mother-infant pairs was 1.96% (18/918). When disaggregated by maternal ART regimen, the lowest seropositivity occurred with dolutegravir (DTG)-based regimens (1.4%) and the highest with protease inhibitor (PI)-based regimens (5.88%). Differences across regimens were not statistically significant (p=0.113). Among maternal factors, age above 35 years (p=0.000) and unsuppressed viral load (p=0.025) were significantly associated with higher seropositivity. Evaluation of Infant-related factors showed that no nevirapine prophylaxis (aOR=43.74; 95% CI: 17.88–106.96; p=0.000), no cotrimoxazole prophylaxis (aOR=11.45; 95% CI: 2.54–51.66; p=0.002), mixed feeding (aOR=26.87; 95% CI: 5.82–124.10; p=0.000) and no breastfeeding (aOR=86.94; 95% CI: 17.40–434.56; p=0.000) were independently associated with MTCT. The maternal model (AIC = 160.09; BIC = 207.19) showed a better fit over the infant model (AIC = 185.91; BIC = 219.99). However, only the infant model identified statistically significant predictors of HIV seropositivity. Conclusions Our findings encourage maintaining similar regimens during pregnancy and breastfeeding unless clinically indicated. While maternal ART regimen and viral load suppression are key in reducing MTCT, infant-related factors such as prophylaxis and feeding practices more strongly predict infant HIV risk. Integrated PMTCT approaches must ensure sustained scale up of ART, maternal viral suppression, promote exclusive breastfeeding, and guarantee infant prophylaxis to achieve the goal of eliminating paediatric HIV.

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